crossing96/oncoscreening huggingface dataset:
Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer.	To disclose the molecular mechanism of bladder cancer, the second most common genitourinary tumor, we had previously done genome-wide expression profile analysis of 26 bladder cancers by means of cDNA microarray representing 27,648 genes. Among genes that were significantly up-regulated in the majority of bladder cancers, we here report identification of M-phase phosphoprotein 1 (MPHOSPH1) as a candidate molecule for drug development for bladder cancer. Northern blot analyses using mRNAs of normal human organs and cancer cell lines indicated this molecule to be a novel cancer-testis antigen. Introduction of MPHOSPH1 into NIH3T3 cells significantly enhanced cell growth at in vitro and in vivo conditions. We subsequently found an interaction between MPHOSPH1 and protein regulator of cytokinesis 1 (PRC1), which was also up-regulated in bladder cancer cells. Immunocytochemical analysis revealed colocalization of endogenous MPHOSPH1 and PRC1 proteins in bladder cancer cells. Interestingly, knockdown of either MPHOSPH1 or PRC1 expression with specific small interfering RNAs caused a significant increase of multinuclear cells and subsequent cell death of bladder cancer cells. Our results imply that the MPHOSPH1/PRC1 complex is likely to play a crucial role in bladder carcinogenesis and that inhibition of the MPHOSPH1/PRC1 expression or their interaction should be novel therapeutic targets for bladder cancers.	bladder
[Intravesical therapy: Influence on superficial bladder cancer recurrence].	OBJECTIVES: To review the influence of various intravesical treatments on superficial bladder cancer recurrence. METHODS: We retrospectively reviewed 473 superficial bladder neoplasias. Based on diagnosis and transurethral resection of bladder tumor (TUR BT), and depending on pathology, we proposed different adjuvant treatment and follow-up schemes. RESULTS: The following factors were independent risk factors for a longer recurrence-free time: intravesical instillations, high dose BCG, and maintenance therapy in comparison to induction. CONCLUSIONS: The use of intravesical instillations independently increases the time to recurrence. It was demonstrated that recurrence was significantly later when high dose BCG and maintenance therapy were employed.	bladder
[Intravesical therapy: Influence on superficial bladder cancer progression].	OBJECTIVES: To review the influence of various intravesical treatments on superficial bladder cancer progression. METHODS: We retrospectively reviewed 473 superficial bladder neoplasias. Based on diagnosis and transurethral resection of bladder tumor (TUR BT), and depending on pathology, we proposed different treatment and follow-up schemes, with BCG in 139 cases and intravesical chemotherapy, mainly Mytomicin C, in 80. RESULTS: Overall, the use or not of bladder instillations did not show statistically significant differences in time to progression. The use of intravesical therapy and maintenance therapy was an independent risk factor for disease-free time to progression when compared with induction. CONCLUSIONS: The use of maintenance intravesical therapy with BCG resulted in a delayed progression of superficial bladder cancer, so that it seems the most effective treatment, mainly in moderate-high risk tumors.	bladder
Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens.	OBJECTIVES: To investigate the relationship between prostate-specific antigen (PSA) level and tumour volume for incidental adenocarcinoma of the prostate found in cystoprostatectomy (CP) specimens, and to analyse the incidence of clinically significant prostate cancers in CP specimens and the biochemical recurrence of incidental prostate cancers on short-term follow up. PATIENTS AND METHODS: Complete data from 97 of 105 prostates from CP specimens were available. Prostates were thoroughly analysed and sectioned at 2 mm intervals. PSA levels and the findings at digital rectal examination before surgery were obtained prospectively. None of the patients had any evidence of prostate cancer before CP. RESULTS: Incidental prostate cancer was detected in 58 of 97 (60%) of the CP specimens; of these, 31 (53%) were significant according to the definition of Stamey et al. There was a weak correlation between tumour volume and PSA level, weighted solely by the four larger-volume cancers. The median PSA level for patients with and without prostate cancer was not significantly different (3.1 vs 1.1 ng/mL, P = 0.06). The follow-up of the 35 patients alive with prostate cancer showed four PSA recurrences (PSA >0.02 ng/mL) with one distant metastasis after a median follow-up of 3 years. None of the patients with insignificant tumours developed biochemical recurrence. CONCLUSIONS: The weak correlation between PSA level and tumour volume in these patients supports the argument that PSA is largely produced by benign prostatic hyperplasia and is therefore a poor screening tool for asymptomatic healthy men. Most incidental prostate cancers in CP specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome.	bladder
Promoter hypermethylation identifies progression risk in bladder cancer.	PURPOSE: New methods to accurately predict an individual tumor behavior are urgently required to improve the treatment of cancer. We previously found that promoter hypermethylation can be an accurate predictor of bladder cancer progression, but it is not cancer specific. Here, we investigate a panel of methylated loci in a prospectively collected cohort of bladder tumors to determine whether hypermethylation has a useful role in the management of patients with bladder cancer. EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR was done at 17 gene promoters, suspected to be associated with tumor progression, in 96 malignant and 30 normal urothelial samples. Statistical analysis and artificial intelligence techniques were used to interrogate the results. RESULTS: Using log-rank analysis, five loci were associated with progression to more advanced disease (RASSF1a, E-cadherin, TNFSR25, EDNRB, and APC; P < 0.05). Multivariate analysis revealed that the overall degree of methylation was more significantly associated with subsequent progression and death (Cox, P = 0.002) than tumor stage (Cox, P = 0.008). Neuro-fuzzy modeling confirmed that these five loci were those most associated with tumor progression. Epigenetic predictive models developed using artificial intelligence techniques identified the presence and timing of tumor progression with 97% specificity and 75% sensitivity. CONCLUSION: Promoter hypermethylation seems a reliable predictor of tumor progression in bladder cancer. It is associated with aggressive tumors and could be used to identify patients with either superficial disease requiring radical treatment or a low progression risk suitable for less intensive surveillance. Multicenter studies are warranted to validate this marker.	bladder
Gene expression profiling of chemically induced rat bladder tumors.	A variety of genetic alterations and gene expression changes are involved in the pathogenesis of bladder tumors. To explore expression changes in 4-hydroxybutyl(butyl)nitrosamine-induced rat bladder tumors, microarray analysis was performed. Analysis yielded 1,138 known genes and 867 expressed sequence tags that were changed when comparing tumors to normal rat epithelia. Altered genes included cell cycle-related genes, EGFR-Ras signaling genes, apoptosis genes, growth factors, and oncogenes. Using the pathway visualization tool GenMAPP, we found that these genes can be grouped along several pathways that control apoptosis, cell cycle, and integrin-mediated cell adhesion. When comparing current data with previous mouse bladder tumor data, we found that > 280 of the same known genes were differentially expressed in both mouse and rat bladder tumors, including cell cycle-related genes, small G proteins, apoptosis genes, oncogenes, tumor-suppressor genes, and growth factors. These results suggest that multiple pathways are involved in rat bladder tumorigenesis, and a common molecular mechanism was found in both rat and mouse bladder tumors.	bladder
Robotic-assisted laparoscopic radical cystoprostatectomy.	OBJECTIVES: Recent small case series have been reported for robotic-assisted laparoscopic radical cystoprostatectomy. The present literature includes 34 patients who have undergone robotic-assisted cystectomy procedures. We report our initial experience with robotic-assisted laparoscopic radical cystoprostatectomy, describing stepwise the surgical procedure and evaluating perioperative and pathologic outcomes of this novel procedure. METHODS: Twenty men underwent robotic-assisted laparoscopic radical cystoprostatectomy and extracorporeal urinary diversion for clinically localized bladder cancer. The stepwise operative procedure is described in detail. Outcome measures evaluated included operative variables, hospital recovery, pathologic outcomes, and complication rate. Comparisons were made to these gender-matched 24 men who underwent an open procedure during this same period. RESULTS: Mean age was 62.3 yr (range: 54-76 yr). Ten patients underwent ileal conduit diversion and 10 patients underwent an orthotopic neobladder. In all cases the urinary diversion was performed extracorporeally. Mean operating room time of all patients was 6.1h (most recent 10 cases, 5.2h). Mean surgical blood loss was 313 ml. On surgical pathology, 14 patients were < or =pT2, 4 patients pT3, and 2 patients N+. In no case was there inadvertent entry into the bladder or positive surgical margins. Mean number of lymph nodes removed was 19 (range: 6-29). Mean time to flatus was 2.1 d and bowel movement 2.8 d. Sixteen patients were discharged on postoperative day (POD) 4, three patients on POD 5, and one on POD 8. There were six postoperative complications (30%) in five patients. CONCLUSIONS: Our initial experience with robotic-assisted laparoscopic radical cystoprostatectomy appears to be favorable with acceptable operative, pathologic, and short-term clinical outcomes. As our experience increases, we should expect to continue to refine our surgical technique and reduce operating room times. Larger experiences are required to adequately evaluate and validate this procedure as an appropriate surgical and oncologic option for the bladder cancer patient.	bladder
Changes in serum sodium concentration after transurethral procedures.	The aim of this study is to evaluate the changes in serum sodium concentration and the degree of correlation with factors such as the amount of intravenous fluid intake, the kind and the amount of irrigating fluids and the duration of the procedure. In this framework, 98 male patients who underwent transurethral procedure were studied and the correlation between the magnitude of hyponatraemia and the above-mentioned parameters was evaluated. All procedures were performed under spinal anesthesia and a solution of either manitol-sorbitol or sterilized water was used as irrigation fluid. Serum sodium concentration was measured before and after the procedure, while the kind and amount of the irrigating fluids, the amount of fluid intake and the duration of the procedure were also recorded. The patients were divided into three groups according to the duration of the procedure (i) <30 min, (ii) 30-60 min, and (iii) >60 min. Significant reduction in serum sodium concentration was found postoperatively (P < 0.001) and this was more profound in procedures longer than 1 h. This reduction was strongly correlated only with the duration of the transurethral procedure (P < 0.01). In conclusion, in transurethral procedures the reduction in serum sodium is postoperatively related to the duration of the procedure, while the intravenous and irrigating fluids to play no role on it.	bladder
Radical cystectomy for primary bladder malignancy: a 10 year review.	BACKGROUND: Radical cystectomy is universally accepted as the definitive treatment for muscle invasive bladder cancer and preventing stage progression in high-risk groups. There are few recent reviews outside of major international centres. We compared our institution's results with published literature. METHODS: Records of 50 consecutive patients treated with radical cystectomy for biopsy-proven bladder carcinoma between 1995 and 2005 were reviewed. RESULTS: The mean age was 70 years and 76% were male. Median follow up was 38 months (1-111 months). Twenty-three patients (46%) had known history of superficial transitional cell carcinoma and 12 patients (24%) had undergone previously intravesical therapy. Transitional cell carcinomas accounted for 94% of cases and most (76%) were poorly differentiated. Twenty-four (48%) had disease at pT3 stage or higher. Regional lymph nodes were involved in 35%. Twenty-three patients (46%) developed recurrence and over half (12 patients) recurred within 12 months. Both lymph node involvement and recurrence were associated with higher pT stage (P < 0.001). All patients with recurrent disease were dead within a year (median 103 days). Median hospital stay was 19 days and there was one postoperative death (2%). Five-year disease-free and overall survival were 42 and 34% respectively. CONCLUSION: Survival following curative resection for primary bladder malignancy is at best modest. Our overall proportion of higher stage disease contributed to earlier recurrence and lower survival rates. Our postoperative morbidity and mortality rates as well as length of stay are acceptable compared with major international units.	bladder
Point and interval estimates of partial population attributable risks in cohort studies: examples and software.	The concept of the population attributable risk (PAR) percent has found widespread application in public health research. This quantity describes the proportion of a disease which could be prevented if a specific exposure were to be eliminated from a target population. We present methods for obtaining point and interval estimates of partial PARs, where the impact on disease burden for some presumably modifiable determinants is estimated in, and applied to, a cohort study. When the disease is multifactorial, the partial PAR must, in general, be used to quantify the proportion of disease which can be prevented if a specific exposure or group of exposures is eliminated from a target population, while the distribution of other modifiable and non-modifiable risk factors is unchanged. The methods are illustrated in a study of risk factors for bladder cancer incidence (Michaud DS et al., New England J Med 340 (1999) 1390). A user-friendly SAS macro implementing the methods described in this paper is available via the worldwide web.	bladder
Long-term survival after gemcitabine and cisplatin in patients with locally advanced transitional cell carcinoma of the bladder: focus on supplementary treatment strategies.	"OBJECTIVE: The objective was to evaluate response and survival, as well as efficacy of subsequent supplementary treatment and follow-up strategy in patients with locally advanced transitional cell carcinoma of the bladder following combination chemotherapy with gemcitabine and cisplatin (GC). METHODS: A total of 84 patients with locally advanced (T4b, Nx, M0 or Tx, N2-3, M0) received GC. After chemotherapy, the strategy was close surveillance in patients with complete response, and supplementary radical cystectomy or radiotherapy whenever possible in patients with partial response. RESULTS: A total of 25 patients (29.8%) with complete response to chemotherapy were followed by close surveillance. This group achieved a median overall survival of 47.6 mo. Another 25 patients had partial response to chemotherapy. Of these patients, 16 had supplementary treatment, with 10 achieving ""no evidence of disease"" (NED). Thus, a total of 35 patients achieved NED with a median overall survival of 48.7 mo versus 10.2 mo in patients not achieving NED (hazard ratio=0.10; 95%CI, 0.05-0.20; p<0.0001). The rate of NED was higher in the group of patients who had a cystectomy compared with the group who received radiotherapy as supplementary treatment. CONCLUSIONS: In patients with locally advanced bladder cancer, NED following chemotherapy alone or chemotherapy plus supplementary cystectomy or radiotherapy is essential to achieve long-term survival. Patients with a partial response should be offered radical cystectomy whenever possible, which seems to be superior to radiotherapy. Close surveillance may be an alternative to immediate cystectomy in patients with complete response following chemotherapy."	bladder
Multimodality bladder preservation therapy for muscle-invasive bladder tumors.	The standard treatment for muscle-invasive bladder cancer in the United States is still radical cystectomy with pelvic lymph node dissection. An alternative to cystectomy is multimodality bladder preservation with thorough transurethral resection, chemotherapy, and radiation therapy. This report addresses several key issues to be considered when selecting patients for a multimodality treatment for invasive bladder cancer. Recent protocols incorporating various fractionation schemes for radiation and alternative chemotherapeutic agents are reviewed. Quality of life associated with bladder preservation after a multimodality approach is also discussed.	bladder
The direct effect of nuclear pores on nuclear chemotherapeutic concentration in multidrug resistant bladder cancer: the nuclear sparing phenomenon.	PURPOSE: Multidrug resistance commonly limits effectiveness in treating malignancy with chemotherapy. Multidrug resistance has classically been described as a cell membrane phenomenon. Multidrug resistant cells are known to specifically exclude chemotherapy from the nucleus, resulting in lower nuclear concentrations than in the cytoplasm. This phenomenon is known as nuclear sparing and little is known of its etiology. We hypothesized that a component of the nuclear membrane, the nuclear pore, is responsible for this phenomenon. MATERIALS AND METHODS: In this in vitro study we used the drug sensitive urothelial cancer cell line Massachusetts General Hospital urothelial 1 sensitive and its multidrug resistant subline Massachusetts General Hospital urothelial 1 resistant. After quantitative assessment of nuclear pores resistant and sensitive cells were fused using polyethylene glycol and laser scanning confocal microscopy was used to identify if drug resistant and sensitive nuclei can coexist within the same cell. The effect of inhibiting nuclear pore function using the specific pore inhibitor, wheat germ agglutinin, was assessed in whole cells using confocal microscopy and cytotoxicity assay as well as in isolated nuclei. RESULTS: Nuclear pores appeared more numerous in multidrug resistance cells. Cell fusion experiments showed that multidrug resistance and sensitive nuclei could coexist with the same cell milieu. Wheat germ agglutinin reversed multidrug resistance in whole cells and isolated nuclei. CONCLUSIONS: Multidrug resistance is a complex phenomenon occurring at many cellular levels, of which all may be potential therapeutic targets. The nuclear pore is involved in this process, which is to our knowledge a previously undescribed phenomenon. These experiments suggest that it may act to export drug from the nucleus, which is a process inhibited by wheat germ agglutinin.	bladder
Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI).	BACKGROUND: Health-related quality of life (HRQOL) has not been adequately measured in bladder cancer. A recently developed reliable and disease-specific quality of life instrument (Bladder Cancer Index, BCI) was used to measure urinary, sexual, and bowel function and bother domains in patients with bladder cancer managed with several different interventions, including cystectomy and endoscopic-based procedures. METHODS: Patients with bladder cancer were identified from a prospective bladder cancer outcomes database and contacted as part of an Institutional Review Board-approved study to assess treatment impact on HRQOL. HRQOL was measured using the BCI across stratified treatment groups. Bivariate and multivariable analyses adjusted for age, gender, income, education, relationship status, and follow-up time were performed to compare urinary, bowel, and sexual domains between treatment groups. RESULTS: In all, 315 bladder cancer patients treated at the University of Michigan completed the BCI in 2004. Significant differences were seen in mean BCI function and bother scores between cystectomy and native bladder treatment groups. In addition, urinary function scores were significantly lower among cystectomy patients treated with continent neobladder compared with those treated with ileal conduit (all pairwise P<.05). CONCLUSIONS: The BCI is responsive to functional and bother differences in patients with bladder cancer treated with different surgical approaches. Significant differences between therapy groups in each of the urinary, bowel, and sexual domains exist. Among patients treated with orthotopic continent urinary diversion, functional impairments related to urinary incontinence and lack of urinary control account for the low observed urinary function scores.	bladder
Nephrotic syndrome as a complication of intravesical BCG treatment of transitional cell carcinoma of urinary bladder.	Nephrotic syndrome can be associated with various neoplasms, especially solid tumors and lymphomas. This patient presented with painless hematuria of transitional cell carcinoma of urinary bladder, underwent transurethral resection, but developed recurrence 16 months later. Repeat resection was done and intravesical Bacillus Calmette-Guerin (BCG) injections were started. After six months, the patient developed hypertension and nephrotic syndrome with a biopsy revealing membranous glomerulonephritis, though there was no radiological evidence of tumor. This is the first case of nephrotic syndrome with intravesical BCG instillation in a bladder carcinoma patient.	bladder